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Distinctive topology of age-associated epigenetic drift in the human interactome

West, J; Widschwendter, M; Teschendorff, AE; (2013) Distinctive topology of age-associated epigenetic drift in the human interactome. PNAS (Proceedings of the National Academy of Sciences of the United States of America) , 110 (35) pp. 14138-14143. 10.1073/pnas.1307242110. Green open access

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Abstract

Recently, it has been demonstrated that DNA methylation, a covalent modification of DNA that can regulate gene expression, is modified as a function of age. However, the biological and clinical significance of this age-associated epigenetic drift is unclear. To shed light on the potential biological significance, we here adopt a systems approach and study the genes undergoing age-associated changes in DNA methylation in the context of a protein interaction network, focusing on their topological properties. In contrast to what has been observed for other age-related gene classes, including longevity- and disease-associated genes, as well as genes undergoing age-associated changes in gene expression, we here demonstrate that age-associated epigenetic drift occurs preferentially in genes that occupy peripheral network positions of exceptionally low connectivity. In addition, we show that these genes synergize topologically with disease and longevity genes, forming unexpectedly large network communities. Thus, these results point toward a potentially distinct mechanistic and biological role of DNA methylation in dictating the complex aging and disease phenotypes.

Type: Article
Title: Distinctive topology of age-associated epigenetic drift in the human interactome
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.1307242110
Publisher version: http://dx.doi.org/10.1073/pnas.1307242110
Language: English
Additional information: © 2013 National Academy of Sciences. PNAS (Proceedings of the National Academy of Sciences)has given a special exception allowing us to deposit the publisher (National Academy of Sciences) PDF in Discovery.
Keywords: Aging, Biological networks, Epigenomics, Network topology
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/1401359
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